Vitamins B6, B9 (Folate), B12

Our rating
Folate (B9) to boost the effect of antidepressant medication 1 smiley:  This treatment is promising and may be useful. It has some evidence to support it, but more evidence is needed to be sure it works.
Vitamin B6, Folate (B9) and B12 as a standalone treatment Question mark:  This treatment has not been properly researched. It is not possible to say whether it is useful or not.

What is it?

Vitamins support normal growth, development and cell functions. All B vitamins help convert carbohydrates into a source of energy (glucose). They assist in the formation of red blood cells.

How does it work?

It is thought that B vitamins may affect depression in these ways:

  • Some people with depression have been found to have low levels of folate (B9)
  • Vitamin B6, folate (B9) and B12 can change levels of brain chemicals that affect mood (such as serotonin and norepinephrine).
  • SAMe is a natural chemical in the body that may help depression. Folate (B9) and vitamin B12 are involved in the production of SAMe.
  • Vitamin B12 helps maintain the insulation around brain cells. The insulation helps brain cells to communicate.

Is it effective?

There is very little scientific evidence on vitamin B6 and B12 for the treatment of depression. More studies of better quality are needed.

Some studies found that adding folate (B9) to antidepressant medication was helpful. One trial found folate (B9) was most helpful for people whose symptoms had not fully responded to medication. Folate (B9) as a standalone treatment does not appear to reduce depression symptoms.

Are there any disadvantages?

Some vitamin supplements can be harmful or ineffective if you take the wrong dose. For example, large doses of Vitamin B6 can cause nerve damage. Talk to your health care professional if you are thinking of taking supplements.

One study reported mania symptoms in a participant who was taking folate (B9) (and antidepressants). No other studies of B vitamins and depression have reported side effects. However, it is not clear whether the studies have investigated negative effects. More research is needed on the possible side effects of B vitamins.

Where do you get it?

Vitamins are present naturally in food. You can buy vitamin supplements in health food shops, supermarkets or from chemists. They usually come in tablet, capsule or powder form. Vitamins may also be given as an injection by a doctor.


Folate (B9) may help boost the effects of antidepressants. More research is needed on B vitamins and depression.

Key references

  • Bottiglieri T. Folate, Vitamin B12, and S-Adenosylmethionine. Psychiatric Clinics of North America 2013: 36: 1-13.
  • Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. The American Journal of Psychiatry 2012; 169: 1267-74.
  • Taylor MJ, Carney SM, Goodwin GM, Geddes JR. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. Journal of Psychopharmacology 2004; 18: 251-256.

Last reviewed and updated: 16 March 2016